rs13154178

Variant names:

• chr5-42827999-G-A
• rs13154178
• ENST00000514218.5:c.-13-19633C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000514218.5(SELENOP):​c.-13-19633C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 152,012 control chromosomes in the GnomAD database, including 7,658 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.31 (7658 hom., cov: 32)
• Consequence: SELENOP ENST00000514218.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.741
• Publications: 9 publications found

Genes affected

SELENOP (HGNC:10751): (selenoprotein P) This gene encodes a selenoprotein that is predominantly expressed in the liver and secreted into the plasma. This selenoprotein is unique in that it contains multiple selenocysteine (Sec) residues per polypeptide (10 in human), and accounts for most of the selenium in plasma. It has been implicated as an extracellular antioxidant, and in the transport of selenium to extra-hepatic tissues via apolipoprotein E receptor-2 (apoER2). Mice lacking this gene exhibit neurological dysfunction, suggesting its importance in normal brain function. Sec is encoded by the UGA codon, which normally signals translation termination. The 3' UTRs of selenoprotein mRNAs contain a conserved stem-loop structure, designated the Sec insertion sequence (SECIS) element, that is necessary for the recognition of UGA as a Sec codon, rather than as a stop signal. The mRNA for this selenoprotein contains two SECIS elements. The use of alternative polyadenylation sites, one located in between the two SECIS elements, results in two populations of mRNAs containing either both (predominant) or just the upstream SECIS element (PMID:27881738). Alternatively spliced transcript variants have also been found for this gene. [provided by RefSeq, Oct 2018]

ENSG00000286271 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.391 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SELENOP	ENST00000514218.5	c.-13-19633C>T		intron_variant	Intron 1 of 4	5		ENSP00000421626.1
ENSG00000286271	ENST00000651306.1	n.377+10648G>A		intron_variant	Intron 2 of 5
ENSG00000286271	ENST00000653383.1	n.273+14080G>A		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46381 AN: 151892 Hom.: 7630 Cov.: 32

Gnomad AFR AF: 0.395

Gnomad AMI AF: 0.423

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.0202

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.325

Gnomad MID AF: 0.303

Gnomad NFE AF: 0.293

Gnomad OTH AF: 0.310

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.306 AC: 46452 AN: 152012 Hom.: 7658 Cov.: 32 AF XY: 0.300 AC XY: 22322 AN XY: 74324

African (AFR) AF: 0.396 AC: 16391 AN: 41392

American (AMR) AF: 0.236 AC: 3601 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.310 AC: 1075 AN: 3468

East Asian (EAS) AF: 0.0202 AC: 105 AN: 5188

South Asian (SAS) AF: 0.162 AC: 782 AN: 4826

European-Finnish (FIN) AF: 0.325 AC: 3433 AN: 10568

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.293 AC: 19941 AN: 67966

Other (OTH) AF: 0.307 AC: 648 AN: 2110

Alfa AF: 0.292 Hom.: 20749

Bravo AF: 0.304

Asia WGS AF: 0.0940 AC: 330 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.58
DANN	Benign	0.36
PhyloP100		-0.74

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs13154178; hg19: chr5-42828101;